Numerous studies have shown that macrophages can orchestrate the microenvironment from the early stage of wound healing to the later stages of scar formation. However, few reviews have highlighted the significance of macrophages during the formation of abnormal scars. The purpose of this review was to outline the polarization of macrophages from early to late stage of pathological scar formation, focusing on spatiotemporal diversity of M1 and M2 macrophages. In this review, the role of macrophages in the formation of hypertrophic scars and keloids is summarized in detail. First, an increased number of M2 cells observed before injuries are significantly associated with susceptibility to abnormal scar pathogenesis. Second, decreased expression of M1 at the early stage and delayed expression of M2 at the late stage results in pathological scar formation. Third, M2 cells are highly expressed at both the margin and the superficial region, which is consistent with the invasive property of keloids. Finally, this review helps to characterize strategies for the prediction and prevention of pathological scar formation.
We developed a stromal cell–derived factor‐1 alpha (SDF‐1α)‐aligned silk fibroin (SF)/three‐dimensional porous bladder acellular matrix graft (3D‐BAMG) composite scaffold for long‐section ventral urethral regeneration and repair in vivo. SDF‐1α‐aligned SF microfiber/3D‐BAMG, aligned SF microfiber/3D‐BAMG, and nonaligned SF microfiber/3D‐BAMG scaffolds were prepared using electrostatic spinning and wet processing. Adipose‐derived stem cell (ADSC) and bone marrow stromal cell (BMSC) migration was assessed in the SDF‐1α‐loaded scaffolds. Sustained SDF‐1α release in vitro and vivo was analyzed using enzyme‐linked immunosorbent assay (ELISA) and western blotting, respectively. The scaffolds were used to repair a 1.5 × 1 cm2 ventral urethral defect in male rabbits in vivo. General observation and retrograde urinary tract contrast assessment were used to examine urethral lumen patency and continuity at 1 and 3 months post‐surgery. Postoperative rehabilitation was evaluated using histological detection. The composite scaffolds sustained SDF‐1α release for over 16 days in vitro. SDF‐1α‐aligned SF nanofiber promoted regeneration of urethral mucosa, submucosal smooth muscles, and microvasculature, increased cellular proliferation, and reduced collagen deposition. SDF‐1α expression was increased in reconstructed urethra at 3 months post‐surgery in SDF‐1α‐aligned SF group. SDF‐1α‐aligned SF microfiber/3D‐BAMG scaffolds may be used to repair and reconstruct long urethral defects because they accelerate urethral regeneration.
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